Enzyme-Triggered Disassembly of Polymeric Micelles by Controlled Depolymerization via Cascade Cyclization for Anticancer Drug Delivery.
ACS Appl Mater Interfaces
; 13(7): 8060-8070, 2021 Feb 24.
Article
em En
| MEDLINE
| ID: mdl-33576220
ABSTRACT
The high activity of specific enzymes in cancer has been utilized in cancer diagnosis, as well as tumor-targeted drug delivery. NAD(P)Hquinone oxidoreductase-1 (NQO1), an overexpressed enzyme in certain tumor types, maintains homeostasis and inhibits oxidative stress caused by elevated reactive oxygen species (ROS) in tumor cells. The activity of NQO1 in lung and liver cancer cells is increased compared to that in normal cells. Interestingly, NQO1 reacts with trimethyl-locked quinone propionic acid (QPA) and produces a lactone-based group via intramolecular cyclization. Toward this objective, we synthesized an amphiphilic block copolymer (QPA-P) composed of NQO1 enzyme-triggered depolymerizable QPA-locked polycaprolactone (PCL) and poly(ethylene glycol) (PEG) as hydrophobic and hydrophilic constituents, respectively. This QPA-P formed self-assembled micelles in aqueous conditions. It was observed that NQO1 catalyzed the depolymerization of QPA-locked PCL via a cascade two-step cyclization process, which eventually induced the dissociation of micellar structure and triggered the release of loaded drugs at the target cancer cells. Compared to the control group, the NQO1-responsive micelle showed NQO1-triggered intracellular drug release and enhanced anticancer effects. These results indicate that the NQO1-responsive polymeric micelles present a promising potential for improving therapeutic efficacy of an anticancer drug delivery system.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polímeros
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Doxorrubicina
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NAD(P)H Desidrogenase (Quinona)
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Sistemas de Liberação de Medicamentos
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Neoplasias Pulmonares
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Antibióticos Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article